Symptoms Improve After a Yoga Program Designed for PTSD in a Randomized Controlled Trial With Veterans and Civilians

Objective: Although yoga shows promise as a treatment for posttraumatic stress disorder (PTSD), there are few randomized controlled trials that demonstrate significant benefits for individuals with PTSD. The present study addresses this need by comparing the effects of a holistic yoga program (HYP) to that of a wellness lifestyle program (WLP) on PTSD symptom severity with a randomized clinical trial. Method: The sample consisted of 209 participants (91.4% veterans; 66% male; 61.7% White) who met diagnostic criteria for PTSD at baseline. Participants were randomly assigned to attend one of the 2 weekly interventions for 16 weeks. The HYP consisted of yoga instruction, while the WLP consisted of didactics, discussions, and walking. PTSD severity was measured using the Clinician Administered PTSD Scale (CAPS-5) and the PTSD Checklist (PCL-5). Results: Analyses revealed that the HYP reduced PTSD severity measured by the CAPS-5 significantly more than the WLP at treatment end (mean difference = −5.4, effect size = 0.46, p < .001), but not at 7-month follow up (mean difference = −0.9, p = .603). Similarly, the HYP reduced PTSD severity measured by the PCL-5 significantly more than the WLP at treatment end (difference = −6.0, p = .001), but not at 7-month follow up (mean difference = −1.0, p = .682). Conclusion: Yoga may be an effective intervention for PTSD in addition to standard treatments. Future yoga trials should consider adding a social component to interventions or booster classes to maintain effects long term

The microbiota-gut-brain axis

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders

Accuracy of the Mologic COVID-19 rapid antigen test: a prospective multi-centre analytical and clinical evaluation

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the reliance on antigen detection rapid diagnostic tests (Ag-RDTs). Their evaluation at point of use is a priority. Methods: Here, we report a multi-centre evaluation of the analytical sensitivity, specificity, and clinical accuracy of the Mologic COVID-19 Ag-RDT by comparing to reverse transcriptase polymerase chain reaction (RT-qPCR) results from individuals with and without COVID-19 symptoms. Participants had attended hospitals in Merseyside, hospital and ambulance services in Yorkshire, and drive-through testing facilities in Northumberland, UK. Results: The limit of detection of the Mologic COVID-19 Ag-RDT was 5.0 x 102 pfu/ml in swab matrix with no cross-reactivity and interference for any other pathogens tested. A total of 347 participants were enrolled from 26th of November 2020 to 15th of February 2021 with 39.2% (CI 34.0-44.6) testing RT-qPCR positive for SARS-CoV-2. The overall sensitivity and specificity of the Mologic Ag-RDT compared to the reference SARS-CoV-2 RT-qPCR were 85.0% (95% CI 78.3-90.2) and 97.8% (95.0-99.3), respectively. Sensitivity was stratified by RT-qPCR cycle threshold (Ct) and 98.4% (91.3-100) of samples with a Ct less than 20 and 93.2% (86.5-97.2) of samples with a Ct less than 25 were detected using the Ag-RDT. Clinical accuracy was stratified by sampling strategy, swab type and clinical presentation. Mologic COVID-19 Ag-RDT demonstrated highest sensitivity with nose/throat swabs compared with throat or nose swabs alone; however, the differences were not statistically significant. Conclusions: Overall, the Mologic test had high diagnostic accuracy across multiple different settings, different demographics, and on self-collected swab specimens. These findings suggest the Mologic rapid antigen test may be deployed effectively across a range of use settings

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Extralymphoid CD8+ T Cells Resident in Tissue from Simian Immunodeficiency Virus SIVmac239Δnef-Vaccinated Macaques Suppress SIVmac239 Replication Ex Vivo▿

Live-attenuated vaccination with simian immunodeficiency virus (SIV) SIVmac239Δnef is the most successful vaccine product tested to date in macaques. However, the mechanisms that explain the efficacy of this vaccine remain largely unknown. We utilized an ex vivo viral suppression assay to assess the quality of the immune response in SIVmac239Δnef-immunized animals. Using major histocompatibility complex-matched Mauritian cynomolgus macaques, we did not detect SIV-specific functional immune responses in the blood by gamma interferon (IFN-γ) enzyme-linked immunospot assay at select time points; however, we found that lung CD8+ T cells, unlike blood CD8+ T cells, effectively suppress virus replication by up to 80%. These results suggest that SIVmac239Δnef may be an effective vaccine because it elicits functional immunity at mucosal sites. Moreover, these results underscore the limitations of relying on immunological measurements from peripheral blood lymphocytes in studies of protective immunity to HIV/SIV

Testing the Effectiveness of 3D Film for Laboratory-Based Studies of Emotion

<div><p>Research in psychology and affective neuroscience often relies on film as a standardized and reliable method for evoking emotion. However, clip validation is not undertaken regularly. This presents a challenge for research with adolescent and young adult samples who are exposed routinely to high-definition (HD) three-dimensional (3D) stimuli and may not respond to older, validated film clips. Studies with young people inform understanding of emotional development, dysregulated affect, and psychopathology, making it critical to assess whether technological advances improve the study of emotion. In the present study, we examine whether 3D film is more evocative than 2D using a tightly controlled within-subjects design. Participants (<i>n</i>  =  408) viewed clips during a concurrent psychophysiological assessment. Results indicate that both 2D and 3D technology are highly effective tools for emotion elicitation. However, 3D does not add incremental benefit over 2D, even when individual differences in anxiety, emotion dysregulation, and novelty seeking are considered.</p></div

Local polynomial smoothed plots of EDA, PEP, and RSA in 2D and 3D during the first presentation of <i>My Bloody Valentine</i>.

<p>Values on the Y-axis represent physiological reactivity (i.e., baseline scores subtracted from task scores). Shading depicts 95% confidence intervals.</p

MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques

The importance of a broad CD8-T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. Here we examined viral loads in SIV-infected MHC homozygous and heterozygous Mauritian cynomolgus macaques (MCM). Chronic viremia in MHC homozygous macaques was 80-fold greater than in MHC heterozygous macaques. Virus from MHC homozygous macaques accumulated 11 to 14 variants consistent with escape from CD8-TL responses after one year of SIV infection. The pattern of mutations detected in MHC heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines

Infection with “Escaped” Virus Variants Impairs Control of Simian Immunodeficiency Virus SIVmac239 Replication in Mamu-B*08-Positive Macaques▿ †

An understanding of the mechanism(s) by which some individuals spontaneously control human immunodeficiency virus (HIV)/simian immunodeficiency virus replication may aid vaccine design. Approximately 50% of Indian rhesus macaques that express the major histocompatibility complex (MHC) class I allele Mamu-B*08 become elite controllers after infection with simian immunodeficiency virus SIVmac239. Mamu-B*08 has a binding motif that is very similar to that of HLA-B27, a human MHC class I allele associated with the elite control of HIV, suggesting that SIVmac239-infected Mamu-B*08-positive (Mamu-B*08+) animals may be a good model for the elite control of HIV. The association with MHC class I alleles implicates CD8+ T cells and/or natural killer cells in the control of viral replication. We therefore introduced point mutations into eight Mamu-B*08-restricted CD8+ T-cell epitopes to investigate the contribution of epitope-specific CD8+ T-cell responses to the development of the control of viral replication. Ten Mamu-B*08+ macaques were infected with this mutant virus, 8X-SIVmac239. We compared immune responses and viral loads of these animals to those of wild-type SIVmac239-infected Mamu-B*08+ macaques. The five most immunodominant Mamu-B*08-restricted CD8+ T-cell responses were barely detectable in 8X-SIVmac239-infected animals. By 48 weeks postinfection, 2 of 10 8X-SIVmac239-infected Mamu-B*08+ animals controlled viral replication to <20,000 viral RNA (vRNA) copy equivalents (eq)/ml plasma, while 10 of 15 wild-type-infected Mamu-B*08+ animals had viral loads of <20,000 vRNA copy eq/ml (P = 0.04). Our results suggest that these epitope-specific CD8+ T-cell responses may play a role in establishing the control of viral replication in Mamu-B*08+ macaques